{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:46:08Z","timestamp":1791978368217,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:00:00Z","timestamp":1477526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["DK-095067"],"award-info":[{"award-number":["DK-095067"]}]},{"name":"NIH","award":["R21-AR-065692"],"award-info":[{"award-number":["R21-AR-065692"]}]},{"DOI":"10.13039\/100007820","name":"Alliance for Lupus Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007820","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Increased levels of type I interferon (IFN) and type I IFN\u2013regulated genes are found in patients with systemic lupus erythematosus (SLE) and may be central to its pathogenesis. Mitochondrial antiviral signaling protein (MAVS) is a key regulator of type I IFN that undergoes a dramatic prion\u2010like aggregation and self propagates the activation signal from viral RNA to amplify downstream IFN production. We undertook this study to determine whether such MAVS aggregates might play a role in the sustained increased production of type I IFN in SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells were isolated and mitochondrial extracts were prepared. MAVS aggregation was detected by semidenatured agarose gel electrophoresis and confirmed by immunofluorescence staining. MAVS\u2010associated signaling proteins were analyzed by Western blotting. MAVS aggregation\u2013associated gene expression signature was analyzed by microarray.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In blood cells from 22 of 67 SLE patients, essentially all MAVS was in a high molecular weight aggregated form. None of 6 rheumatoid arthritis patients and only 3 of 33 healthy controls had abnormal MAVS. Compared to MAVS aggregate\u2013negative patients, MAVS aggregate\u2013positive SLE patients had significantly higher serum levels of IFN\u03b2 and significantly increased levels of autoantibodies against Sm and U1 RNP. Gene array data revealed a characteristic gene expression pattern in these patients, with altered expression of genes involved in IFN signaling and membrane trafficking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Persistent MAVS aggregates may lead to increased type I IFN production and result in unmitigated signals leading to autoimmunity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39733","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T20:22:49Z","timestamp":1461615769000},"page":"2697-2707","source":"Crossref","is-referenced-by-count":71,"title":["Prion\u2010like Aggregation of Mitochondrial Antiviral Signaling Protein in Lupus Patients Is Associated With Increased Levels of Type I Interferon"],"prefix":"10.1002","volume":"68","author":[{"given":"Wen\u2010Hai","family":"Shao","sequence":"first","affiliation":[{"name":"Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Shu","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Zhen","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4689-6821","authenticated-orcid":false,"given":"Brendan","family":"Hilliard","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen O.","family":"Priest","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Cesaroni","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny P.\u2010Y.","family":"Ting","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine at Temple University Philadelphia 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